Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis

R Clynes, C Dumitru, JV Ravetch - Science, 1998 - science.org
R Clynes, C Dumitru, JV Ravetch
Science, 1998science.org
The generation of autoantibody and subsequent tissue deposition of immune complexes
(IC) is thought to trigger the pathogenic consequences of systemic autoimmune disease.
Modulation of the autoantibody response disrupts pathogenesis by preventing the formation
of ICs; however, uncoupling IC formation from subsequent inflammatory responses seems
unlikely because of the apparent complexity of the IC-triggered inflammatory cascade.
However, the disruption of a single gene, which encodes the γ chain of the Fc receptor, was …
The generation of autoantibody and subsequent tissue deposition of immune complexes (IC) is thought to trigger the pathogenic consequences of systemic autoimmune disease. Modulation of the autoantibody response disrupts pathogenesis by preventing the formation of ICs; however, uncoupling IC formation from subsequent inflammatory responses seems unlikely because of the apparent complexity of the IC-triggered inflammatory cascade. However, the disruption of a single gene, which encodes the γ chain of the Fc receptor, was found to achieve this uncoupling in a spontaneous model of lupus nephritis, the New Zealand Black/New Zealand White (NZB/NZW) mouse. Gamma chain–deficient NZB/NZW mice generated and deposited IC and activated complement, but were protected from severe nephritis, thus defining another potential pathway for therapeutic intervention in autoimmune disease.
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